Viral load reduction improves activation and function of natural killer cells in

StephenW

My personal opinion only: this research shows viral load reduction could contribute to clearance of the virus.
只是我个人的看法：这项研究显示，病毒载量的减少可能有助于该病毒的清除。

J Hepatol. 2010 Sep 6. [Epub ahead of print]

Viral load reduction improves activation and function of natural killer
cells in patients with chronic hepatitis B.

Tjwa ET, van Oord GW, Hegmans JP, Janssen HL, Woltman AM.
Department of Gastroenterology and Hepatology, Erasmus MC University
Medical Centre, Rotterdam, The Netherlands.

Abstract
BACKGROUND & AIMS: Natural killer (NK) cells play a major role in
anti-viral immunity as first line defense and regulation of virus-specific
T cell responses. This study aimed to investigate phenotype and function
of NK cells in patients with chronic hepatitis B virus (HBV) infection and
to study the effect of anti-viral therapy.

METHODS: Peripheral blood NK cells from 40 chronic HBV patients were
compared to NK cells of 25 healthy controls. The effect of
entecavir-induced viral load reduction on NK cell phenotype and function
was investigated in 15 chronic HBV patients.

RESULTS: NK cell numbers and subset distribution did not differ between
HBV patients and normal subjects. In chronic HBV patients, the cytotoxic
capacity was retained, but NK cell activation and subsequent IFNγ, and
TNFα production, especially of the CD56(dim) subset, were strongly
hampered. This functional dichotomy was paralleled by an altered
activation state, elevated expression of NKG2A, and downregulated
expression of CD16 and NKp30, which correlated with serum HBV-DNA load.
Anti-viral therapy partially restored NK cell phenotype, as shown by NKG2A
downregulation. Moreover, viral replication inhibition improved IFNγ
production as a result of an increased ability of CD56(dim) NK cells to
become activated de novo. This improved NK cell activation and function
which correlated with therapy-induced reduction in serum ALT levels, but
not HBV-DNA load.

CONCLUSIONS: The specific defect in CD56(dim) NK cell activation and the
reduced capacity to produce anti-viral and Th1-skewing cytokines may play
a role in HBV persistence. Restoration of this NK cell cytokine-producing
capacity as achieved by viral load reduction could therefore contribute to
definite clearance of the virus.

Copyright © 2010 European Association for the Study of the Liver.
Published by Elsevier B.V. All rights reserved.
PMID: 21095036 [PubMed - as supplied by publisher]

Ĵ肝脏病杂志。 2010年9月6日。 [EPUB的提前打印]

病毒载量的减少提高了活化自然杀伤和功能
在患者的细胞与慢性乙型肝炎

Tjwa东部，Van Oord提供毛重，Hegmans太平绅士，扬森红莲，Woltman上午。
胃肠病学和肝病学系，Erasmus MC大学
医疗中心，鹿特丹，荷兰。

摘要
背景与目的：自然杀伤（NK）细胞中发挥重要作用
抗病毒免疫作为第一线防御和病毒特异性调控
T细胞的反应。本研究旨在探讨表型和功能
在慢性乙型肝炎病毒（HBV）感染患者的NK细胞和
研究了抗病毒治疗效果。

方法：外周血40例慢性乙型肝炎患者的NK细胞
相对于25名健康对照组NK细胞。的效果
恩替卡韦诱导NK细胞表型和功能的病毒载量减少
调查了15例慢性乙肝患者。

结果：NK细胞亚群数量和分布没有显着差异
乙肝患者和正常人。在慢性乙肝患者中，细胞毒性
容量被保留下来，但NK细胞的活化和随后IFNγ的，并
肿瘤坏死因子的生产尤其是CD56的（点心）子集，得到了强有力的
而受到阻碍。这个功能二分法是平行的一个改变
激活状态，NKG2A的表达升高，并下调
表达CD16和NKp30，与血清HBV - DNA载量呈正相关。
抗病毒治疗部分恢复NK细胞表型，如NKG2A所示
下调。此外，抑制病毒复制IFNγ的改善
作为一个生产的CD56的（点心）对NK细胞的能力增强的结果
从头被激活。这种改进的NK细胞活性和功能
这与治疗相关引起的血清ALT水平降低，但
没有乙肝病毒DNA载量。

结论：在CD56的具体缺陷（点心）和NK细胞的活化
能力下降产生抗病毒及Th1 -倾斜细胞因子可能扮演
在乙肝病毒持续性的作用。本NK细胞因子恢复生产
病毒载量的减少所取得的能力，因此可以作出贡献
明确清理病毒。

版权©为2010年欧洲肝脏研究协会。
B.诉由Elsevier出版的所有权利保留。
结论：21095036 [PubMed的 - 由出版商提供]